High-dose radiation treatment for patients with a few metastatic tumors

Phase III Randomized Controlled Trial and Economic Evaluation of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer (SABR-COMET-3)

This study is testing if a high-dose radiation treatment called SABR can help people with 1-3 metastatic tumors live longer and feel better compared to standard radiation therapy.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 330 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: British Columbia Cancer Agency (Academic / other)
• Drugs / interventions: Chemotherapy, radiation, bevacizumab, immunotherapy, doxorubicin
• Locations: 17 sites (Griffith, New South Wales and 16 other locations)
• Trial ID: NCT03862911 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of Stereotactic Ablative Radiotherapy (SABR) compared to standard palliative radiotherapy in patients with 1-3 metastatic tumors. The trial aims to assess overall survival, progression-free survival, toxicity, and quality of life outcomes. Participants will be randomly assigned to receive either SABR or standard care, with an integrated economic evaluation to analyze cost-effectiveness. Additionally, the study will explore potential biomarkers associated with the oligometastatic state.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 or older with 1-3 current metastases and a controlled primary tumor.

Not a fit: Patients with more than 3 metastases or those who are suitable for surgical resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival and quality of life for patients with oligometastatic cancer.

How similar studies have performed: Previous studies have shown promising results with SABR in similar patient populations, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Total number of 1-3 current metastases, and a maximum 8 lifetime metastases
* Age 18 or older
* Willing to provide informed consent
* ECOG score 0-2
* Life expectancy \>6 months
* Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
* Controlled primary tumor

  * defined as: at least 3 months since original tumor treated definitively, with no progression at primary site (can be considered controlled if no evidence of the primary tumour on imaging)
* A history and physical exam, including ECOG performance status, performed within 6 weeks prior to trial enrollment
* Not suitable for resection at all sites or decline surgery
* Patient has had a CT chest, abdomen and pelvis or PET-CT within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR). CT neck as clinically indicated.
* Patient has had a nuclear bone scan (if no PET-CT) within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR)
* If solitary lung nodule for which biopsy is unsuccessful or not possible, patient has had an FDG PET scan or CT (chest, abdomen, pelvis) and bone scan within 8 weeks prior to enrollment, and with 12 weeks prior to treatment (if randomized to SABR). CT neck as clinically indicated.
* If colorectal primary with rising CEA, but equivocal imaging, patient has had an FDG PET scan within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR)
* Patient has had CT or MRI brain imaging if primary has a propensity for CNS metastasis within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR)
* Patient is judged able to:
* Maintain a stable position during therapy
* Tolerate immobilization device(s) that may be required to deliver SABR safely
* Negative pregnancy test for Women of Child-Bearing potential (WOCBP) within 4 weeks of RT start date
* Patient is able and willing to complete the quality of life questionnaires, and other assessments that are a part of this study, via paper or online using REDCap (if email address is provided by participant on the informed consent)

Waivers to the inclusion criteria will NOT be allowed.

Exclusion Criteria:

* Lesion in femoral bone requiring surgical fixation
* Chemotherapy agents (cytotoxic, or molecularly targeted agents) used within the period of time commencing 2 weeks prior to radiation, lasting until 1 week after the last fraction for patients randomized to SABR
* Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the GI tract will receive radiotherapy, and connective tissue disorders such as lupus or scleroderma.
* Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated with conventional radiation previously, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases should be discussed with one of the study PIs.
* Concurrent malignant cancer, or history of malignant cancers within the past 5 years
* Malignant pleural effusion
* History of poor lung function (if treating near lung)
* History of poor liver function (if treating near liver)
* Inability to treat all sites of disease
* Maximum size of 5 cm for lesions outside the brain, except:

  * Bone metastases over 5 cm may be included, if in the opinion of the local PI it can be treated safely (e.g. rib, scapula, pelvis)
  * Any brain metastasis \>3 cm in size or a total volume of brain metastases greater than 30 cc.
* Clinical or radiologic evidence of spinal cord compression, or epidural tumor within \<2 mm of the spinal cord. Patients can be eligible if surgical resection has been performed, but the surgical site counts toward the total of up to 8 lifetime metastases.
* Dominant brain metastasis requiring surgical decompression
* Pregnant or breastfeeding women

Waivers to exclusion criteria will NOT be allowed.

Where this trial is running

Griffith, New South Wales and 16 other locations

• Cancer Care Griffith — Griffith, New South Wales, Australia (Recruiting)
• Riverina Cancer Care Centre — Wagga Wagga, New South Wales, Australia (Recruiting)
• Alfred Hospital — Melbourne, Victoria, Australia (Recruiting)
• Tom Baker Cancer Centre — Calgary, Alberta, Canada (Recruiting)
• BC Cancer — Kelowna, British Columbia, Canada (Recruiting)
• BC Cancer - Prince George — Prince George, British Columbia, Canada (Recruiting)
• BC Cancer — Surrey, British Columbia, Canada (Recruiting)
• BC Cancer — Vancouver, British Columbia, Canada (Recruiting)
• BC Cancer — Victoria, British Columbia, Canada (Recruiting)
• London Health Sciences Centre — London, Ontario, Canada (Recruiting)
• Walker Family Cancer Centre — Saint Catharines, Ontario, Canada (Recruiting)
• St. Luke's Radiation Oncology Network — Rathgar, Dublin, Ireland (Recruiting)
• Beacon Hospital — Dublin, Sandyford, Ireland (Recruiting)
• Bon Secours Radiotherapy Cork in partnership with UPMC Hillman Cancer Centre — Cork, Ireland (Recruiting)
• Aberdeen Royal Infirmary — Aberdeen, Scotland, United Kingdom (Recruiting)
• Edinburgh Cancer Centre — Edinburgh, Scotland, United Kingdom (Recruiting)
• Beatson West of Scotland Cancer Centre — Glasgow, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Robert A Olson, MD, MSc, FRCPC — BC Cancer Prince George
• Study coordinator: Robert Olson, MD, MSc, FRCPC

Conditions Metastatic Tumors